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Genexpressionssignaturen beim Mammakarzinom

Gene expression signatures in breast cancer

  • Leitthema
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Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Genexpressionssignaturen zeigen die molekulare Heterogenität des Mammakarzinoms. Die ersten Genexpressionssignaturen wurden mit DNA-Microarrays an frisch gefrorenem Tumorgewebe durchgeführt und führten zur Identifikation von sog. intrinsischen Subtypen wie Luminal A, Luminal B, „ERBB2“-like (HER2) und „basal-like“. Alternativ unterteilen andere Genexpressionssignaturen die Patientinnen in geringes und hohes Risiko für eine spätere Metastasierung. Für den praktischen Einsatz ist es wichtig, dass Genexpressionssignaturen auch an formalinfixiertem, in Paraffin eingebettetem Tumorgewebe durchgeführt werden können.

Ziel

Der Beitrag ist ein evidenzbasierter Review mit der Fragestellung nach der prognostischen Bedeutung von Genexpressionssignaturen beim frühen Mammakarzinom.

Material und Methoden

Mittels systematischer Literaturrecherche in Pubmed und manueller Recherche wurden relevante Publikationen zwischen 2000 und 2013 untersucht. Suchbegriffe waren „gene-expression“, „intrinsic subtypes“, „Endopredict“, „Mammaprint“, „Oncotype DX“, „PAM50“, „level of evidence“, „immune system“ in Kombination mit „prognosis“ und „breast cancer“.

Ergebnisse

Um eine falsche Risikoklassifikation und damit eine mögliche Unter- oder Übertherapie der Patientinnen zu vermeiden, müssen sorgfältige klinische und analytische Validierungen sowie ein hoher Level of Evidence (LoE) gefordert werden. Die kommerziell erhältlichen Genexpressionssignaturen der ersten Generation Endopredict® (LoE I), Mammaprint® (LoE II), Oncotype DX® (LoE I) und PAM50 (LoE II) werden von der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) mit +/− bewertet, d. h. sie können in individuellen Fällen durchgeführt werden; derzeit kann allerdings keine allgemeine Empfehlung gegeben werden. Diese Signaturen können eingesetzt werden, um v. a. bei östrogenrezeptorpositiven (ER-positiven) Patientinnen eine genauere Risikoabschätzung zu erreichen. Genexpressionssignaturen der zweiten Generation berücksichtigen demgegenüber Immunzelltranskripte und haben besonders bei ER-negativen und HER2-positiven sowie schnell proliferierenden Mammakarzinomen prognostische Bedeutung.

Schlussfolgerung

Genexpressionssignaturen mit einem hohen LoE können zu einer verbesserten prognostischen Abschätzung beim frühen Mammakarzinom beitragen.

Abstract

Context

Gene expression analysis has depicted the striking molecular heterogeneity in human breast cancer. DNA microarray analyses of fresh-frozen tissue identified several so-called intrinsic subtypes, such as luminal A, luminal B, ERBB2-like (HER2) and basal-like. Alternatively, gene expression signatures were used to distinguish patients with low risk or high risk for distant metastasis. To improve feasibility it is important that these gene expression analyses can be performed utilizing formalin-fixed paraffin-embedded tissue.

Objective

The aim of this evidence-based review was the prognostic significance of gene expression signatures in early breast cancer.

Material and methods

A systematic search in PubMed and a manual search were carried out to review relevant articles published between 2000 and 2013. Key words used were “gene-expression”, “intrinsic subtypes”, “Endopredict”, “Mammaprint”, “Oncotype DX”, “PAM50”, “level of evidence” and “immune system” in combination with “prognosis” and “breast cancer”.

Results

To avoid an inaccurate risk classification it is mandatory that meticulous clinical and analytical validation of these tests is performed and that a high level of evidence (LoE) is achieved. The commercially available gene expression signatures of the first generation, such as Endopredict® (LoE I), Mammaprint® (LoE II), Oncotype DX® (LoE I) and PAM50 (LoE II) are currently rated as +/− by the Working Group on Gynecological Oncology (AGO) suggesting that these tests may be performed only in individual cases and that a general recommendation cannot be given. These signatures can be used for risk classification especially in estrogen receptor (ER) positive patients. In contrast, signatures of the second generation use immune cell-related transcripts to assess prognosis better especially in ER negative or HER2 positive rapidly proliferating breast cancer.

Conclusion

Gene expression signatures with a high LoE can result in an improved assessment of prognosis in early breast cancer.

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehung hin: PD Dr.  Marcus Schmidt ist als Referent für die Firma Sividon tätig.

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  1. Klinik und Poliklinik für Geburtshilfe und Frauenkrankheiten, Universitätsmedizin Mainz, Langenbeckstraße 1, 55131, Mainz, Deutschland

    M. Schmidt

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Correspondence to M. Schmidt.

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Schmidt, M. Genexpressionssignaturen beim Mammakarzinom. Onkologe 19, 465–470 (2013). https://doi.org/10.1007/s00761-013-2447-7

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  • DOI: https://doi.org/10.1007/s00761-013-2447-7

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